Disease relevance of IMPDH2

• Modulation of IMPDH2, survivin, topoisomerase I and vimentin increases sensitivity to methotrexate in HT29 human colon cancer cells [1].
• ZNRD1 mediates resistance of gastric cancer cells to methotrexate by regulation of IMPDH2 and Bcl-2 [2].
• Patients with treatment-related toxicities displayed a trend to a higher level of IMPDH II expression than those without toxicity (mean, 1.126 vs 0.771) [3].

High impact information on IMPDH2

• We evaluated a selection scheme based on the expression of a variant of inosine monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in the de novo purine biosynthesis pathway [4].
• IMPDH 2 messenger RNA (mRNA) and IMPDH protein were both regulated reciprocally by changes in levels of their end-products [5].
• One of these metabolites (M-2), identified as an acyl glucuronide of MPA, was found to inhibit IMPDH-II in vitro [6].
• Assignment1 of inosine '-monophosphate dehydrogenase type 2 (IMPDH2) to human chromosome band 3p21.2 by in situ hybridization [7].
• Among the differentially expressed genes we chose for further validation were inosine monophosphate dehydrogenase type II (IMPDH2), inosine monophosphate cyclohydrolase and survivin as up-regulated genes, and topoisomerase I (TOP1) and vimentin as down-regulated genes [1].

Biological context of IMPDH2

• 2. Two overlapping yeast artificial chromosome clones containing the full gene for type II IMPDH (IMPDH2) were isolated, and a physical map of 117 kb of human genomic DNA in this region of chromosome 3 was constructed [8].
• We found that subunits of complex I and complex III, molecular chaperones, and a protein involved in cell cycle control were downregulated and Inosine 5'-monophosphate dehydrogenase type 2 (IMPDH2) involved in nucleotide biosynthesis was upregulated in rho(0) cells [9].
• Real-time PCR quantitation of IMPDH II gene expression was reliable, sensitive, and specific [3].

Anatomical context of IMPDH2

• CONCLUSIONS: Expression of IMPDH2 is increased in K562 cells upon short treatment with MTX and once resistance to MTX is established [10].
• IMPDH II is necessary for de novo purine synthesis in activated lymphocytes [3].

Associations of IMPDH2 with chemical compounds

• Changes in IMPDH2 mRNA levels were confirmed and functional analyses were performed by inhibiting IMPDH with either benzamide riboside, mycophenolic acid, or tiazofurin [10].
• In vitro and in vivo drug sensitivity analyses revealed that inhibition of ZNRD1 and IMPDH2 activity sensitized SGC7901/VCR cells to methotrexate [2].
• IMPDH2 has low genetic diversity, but the nonsynonymous variant L263F has a significant impact on inosine 5'-monophosphate dehydrogenase activity [11].

Other interactions of IMPDH2

• Chromosomal localization and structure of the human type II IMP dehydrogenase gene (IMPDH2) [8].
• IMPDH II gene expression was assessed using quantitative, real-time PCR and normalized using glyceraldheyde-3-phosphate dehydrogenase (GAPDH) [3].

Analytical, diagnostic and therapeutic context of IMPDH2

• Of the downregulated genes we chose Inosine monophosphate dehydrogenase 2 (IMPDH2) for further validation by quantitative RT-PCR [2].
• Taken together, the findings suggest that ZNRD1 could act as a modulator of methotrexate chemotherapy in gastric cancer cells through the regulation of IMPDH2 and Bcl-2 [2].

References